[Gene mapping and analysis of candidate genes in a Chinese family with autosomal dominant congenital coralliform cataract].

OBJECTIVE

To map and to identify the causal gene of autosomal dominant congenital coralliform cataract (ADCC) in a Chinese family.

METHODS

Case series study. Clinical features of all affected members in this family were examined. Blood samples were collected from nine family members for genetic linkage analysis. Polymorphic microsatellite markers were selected from the regions which harbor all known loci linked with ADCC. Direct genomic sequencing was used to evaluate the candidate gene.

RESULTS

The affected members in this family showed classic phenotype of ADCC. The maximum two-point LOD score of 1.51 was obtained for marker D2S325 (θ = 0). The LOD score of 1.20 was obtained for marker D11S925. The CRYGC/CRYGD gene located on 2q33-q35 and the CRYAB gene located on 11q22-q22.3. Therefore, the CRYGC/CRYGD and CRYAB gene may be the candidate gene in this family. Sequencing of the coding regions of the CRYGD gene showed the presence of a heterozygous C→A transversion at nucleotide 70 in exon 2 of CRYGD that is associated with cataracts in this family. This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterized this protein. No mutation in all exons of CRYGC and CRYAB gene were found in the family.

CONCLUSIONS

Direct DNA sequence analysis revealed a C-to-A transition at nucleotide 70 of the CRYGD gene in this ADCC family.